title: Lung tumor promotion by chromium-containing welding particulate matter in a mouse model.
abstract: BACKGROUND
  Epidemiology suggests that occupational exposure to welding particulate matter (PM) may increase lung cancer risk. However, animal studies are lacking to conclusively link welding with an increased risk. PM derived from stainless steel (SS) welding contains carcinogenic metals such as hexavalent chromium and nickel. We hypothesized that welding PM may act as a tumor promoter and increase lung tumor multiplicity in vivo. Therefore, the capacity of chromium-containing gas metal arc (GMA)-SS welding PM to promote lung tumors was evaluated using a two-stage (initiation-promotion) model in lung tumor susceptible A/J mice.
  
  
  METHODS
  Male mice (n = 28-30/group) were treated either with the initiator 3-methylcholanthrene (MCA;10 μg/g; IP) or vehicle (corn oil) followed by 5 weekly pharyngeal aspirations of GMA-SS (340 or 680 μg/exposure) or PBS. Lung tumors were enumerated at 30 weeks post-initiation.
  
  
  RESULTS
  MCA initiation followed by GMA-SS welding PM exposure promoted tumor multiplicity in both the low (12.1 ± 1.5 tumors/mouse) and high (14.0 ± 1.8 tumors/mouse) exposure groups significantly above MCA/sham (4.77 ± 0.7 tumors/mouse; p = 0.0001). Multiplicity was also highly significant (p < 0.004) across all individual lung regions of GMA-SS-exposed mice. No exposure effects were found in the corn oil groups at 30 weeks. Histopathology confirmed the gross findings and revealed increased inflammation and a greater number of malignant lesions in the MCA/welding PM-exposed groups.
  
  
  CONCLUSIONS
  GMA-SS welding PM acts as a lung tumor promoter in vivo. Thus, this study provides animal evidence to support the epidemiological data that show welders have an increased lung cancer risk.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road MS L2015, Morgantown, WV 26505, USA. paz9@cdc.gov.
authors.forename: Patti C
authors.initials: PC
authors.lastname: Zeidler-Erdely
authors.forename: Terence G
authors.initials: TG
authors.lastname: Meighan
authors.forename: Aaron
authors.initials: A
authors.lastname: Erdely
authors.forename: Lori A
authors.initials: LA
authors.lastname: Battelli
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kashon
authors.forename: Michael
authors.initials: M
authors.lastname: Keane
authors.forename: James M
authors.initials: JM
authors.lastname: Antonini
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D002857:Chromium / Q000633:toxicity*; D003043:Cocarcinogenesis; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D012906:Smoke / Q000009:adverse effects*; D013997:Time Factors; D014896:Welding
chemical_list: D000395:Air Pollutants, Occupational; D012906:Smoke; D002857:Chromium; C074702:chromium hexavalent ion; D008748:Methylcholanthrene